Current and emerging management options for Clostridium difficile infection: what is the role of fidaxomicin?

Until recently, treatment of Clostridium difficile infection (CDI) was mainly limited to oral metronidazole and vancomycin, neither of which is optimal. Up to 25% of patients with CDI experience recurrence of infection within 30 days following treatment with these agents, while c. 45-65% of these patients experience further (and sometimes multiple) recurrences. Recurrent CDI represents a major treatment challenge for which new therapeutic options are sorely needed. Fidaxomicin is a first-in-class, oral macrocyclic antibiotic with targeted bactericidal activity against C. difficile and minimal effect on the constituents of the normal colonic microflora. This microflora-sparing activity allows for more rapid restoration of the normal colonic microflora in patients with CDI. In two separate, but almost identical, phase 3 clinical trials in which patients with CDI were treated with either fidaxomicin or vancomycin, fidaxomicin demonstrated superior clinical outcomes in comparison with the current best available treatment. While non-inferiority was demonstrated with respect to rates of clinical cure at end of treatment, significantly fewer fidaxomicin-treated patients experienced disease recurrence, which translated into clinically significant improvements in sustained clinical cure. Subsequent sub-population analyses suggest that these benefits extend to older patients, patients with severe CDI, renally impaired patients and patients with a prior episode of CDI. For CDI patients receiving concomitant antibiotics, fidaxomicin achieved significantly better rates of clinical cure and sustained clinical cure than vancomycin recipients. Fidaxomicin has a safety profile similar to oral vancomycin and appears generally well tolerated. Fidaxomicin represents an important addition to current treatment options for CDI.